The prior art is deficient in simple, non-invasive and effective methods of identifying molecular markers and the use of said molecular markers for purposes of: diagnosis; prognosis; prediction of disease, stage of disease or disease risk; monitor disease progression and/or regression; monitor disease reoccurrence and identifying risk of disease reoccurrence or the like. The prior art is also deficient in simple non-invasive methods of identifying molecular markers and use of said molecular markers to determine and/or predict response to treatment and/or treatment outcomes, monitor and/or predict treatment compliance or non-compliance, etc. Although progress has been made in identifying molecular markers by detecting the products of putative molecular markers using expression arrays in a variety of diagnostic areas and therapeutic areas, such progress has been primarily limited to studying non-blood tissue samples, such as primary tumors, that are difficult to obtain and thus have limited potential as a diagnostic. What is even more unsatisfactory is that retrieval of such tissue samples often requires invasive medical procedures such as surgery. Prediction of response to treatment is also a significant problem. It is well understood that, for many currently recognized treatments, only a small percentage of the population (for example approximately 20-30%) will respond positively. Amongst the remainder of the population, there are those who do not improve, and others who display a negative or toxic response to the treatment. As a result of these detrimental effects to some, many effective treatments do not get to market. The prior art is thus deficient in simple, non-invasive methods to analyze and predict treatment and response to treatment.
Such drawbacks have made identification of molecular markers unsatisfactorily difficult. See, for example, Alon et al, 1999, Proc. Natl. Acad. Sci. USA 96, pp. 6745-6750; Schummer et al, 1999, Gene 238, pp. 375-385; and van't Veer, 2002, Nature 415, pp. 530-536.
Even where progress has been made in identifying molecular markers by monitoring molecular marker products using expression arrays—whether in blood or using tissue—the techniques utilized merely identify large number of molecular markers two or more of which may be required so as to permit categorizing an unknown sample for diagnosis. It is not clear, however, which of these molecular markers are most useful to accurately diagnose an unknown sample. In addition, techniques currently available in the art are not sufficiently robust (ie high levels of reproducibility) in accordance with scientific and regulatory standards so as to be used reliably to diagnose a test individual. Thus what is required in the art is a means to select smaller subsets of useful molecular markers which when used in combination permit the accurate and reproducible diagnosis of an unknown sample for a particular trait of interest. Further what is required in the art is a means of translating the molecular marker data from these selected combinations so as to convert these into a diagnosis.
Discussion or citation of a reference herein will not be construed as an admission that such reference is prior art to the present invention.